Figure 1.

This cartoon figure illustrates some of the interactions of several neurotransmitter pathways in the Brain Reward Cascade (BRC) system. Environmental stimulation in the hypothalamus causes the release of serotonin, which, in turn, via, for example, 5HT-2a receptors activates (green equals sign) opioid peptides, releasing them into the hypothalamus. The opioid peptides have two distinct effects via two different opioid receptors. The first inhibits (red hash sign) through the mu-opioid receptor (possibly via enkephalin), which projects to the substantia nigra GABAA neurons, and the second stimulates (green equal sign) cannabinoid neurons (e.g., 2-archydonoglcerol and anandamide) through beta-endorphin-linked delta receptors, which, in substantia nigra, inhibit GABAA neurons. Activated cannabinoids, mostly 2-archydonoglcerol, can also disinhibit (red hash sign) substantia nigra GABAA neurons indirectly by activating G1/0-coupled CB1 receptors. Similarly, dorsal raphe nuclei (DRN) glutamate neurons can disinhibit substantia nigra GABAA neurons indirectly through the activation of GLU M3 receptors (red hash sign). Stimulated GABAA neurons will powerfully (red hash signs) inhibit VTA glutaminergic drive via GABAB 3 neurons. VTA glutamate neurons project to dopamine neurons through NMDA receptors (green equals sign), where they preferentially release dopamine at the nucleus accumbens, shown as a bullseye, indicating euphoria (a motivational response).